Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.

Détails

ID Serval
serval:BIB_D9A7084A714B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.
Périodique
Aids
Auteur(s)
Petrovski S., Fellay J., Shianna K.V., Carpenetti N., Kumwenda J., Kamanga G., Kamwendo D.D., Letvin N.L., McMichael A.J., Haynes B.F., Cohen M.S., Goldstein D.B., Center for HIV/AIDS Vaccine Immunology 
ISSN
1473-5571 (Electronic)
ISSN-L
0269-9370
Statut éditorial
Publié
Date de publication
2011
Volume
25
Numéro
4
Pages
513-518
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
Résumé
Objective: To date, CCR5 variants remain the only human genetic factorsto be confirmed to impact HIV-1 acquisition. However, protective CCR5variants are largely absent in African populations, in which sporadicresistance to HIV-1 infection is still unexplained. We investigatedwhether common genetic variants associate with HIV-1 susceptibility inAfricans.Methods: We performed a genome-wide association study (GWAS) in apopulation of 1532 individuals from Malawi, a country with highprevalence of HIV-1 infection. Using single-nucleotide polymorphisms(SNPs) present on the genome-wide chip, we also investigated previouslyreported associations with HIV-1 susceptibility or acquisition.Recruitment was coordinated by the Center for HIV/AIDS VaccineImmunology at two sexually transmitted infection clinics. HIV status wasdetermined by HIV rapid tests and nucleic acid testing.Results: After quality control, the population consisted of 848high-risk seronegative and 531 HIV-1 seropositive individuals. Logisticregression testing in an additive genetic model was performed for SNPsthat passed quality control. No single SNP yielded a significant P valueafter correction for multiple testing. The study was sufficientlypowered to detect markers with genotype relative risk 2.0 or more andminor allele frequencies 12% or more.Conclusion: This is the first GWAS of host determinants of HIV-1susceptibility, performed in an African population. The absence of anysignificant association can have many possible explanations: rarergenetic variants or common variants with weaker effect could beresponsible for the resistance phenotype; alternatively, resistance toHIV-1 infection might be due to nongenetic parameters or to complexinteractions between genes, immunity and environment. (C) 2011 WoltersKluwer Health vertical bar Lippincott Williams & Wilkins
Mots-clé
Adolescent, Adult, African Continental Ancestry Group/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HIV Infections/epidemiology, HIV Infections/genetics, HIV-1, Humans, Type="Geographic">Malawi/epidemiology, Male, Middle Aged, Phenotype, Receptors, CCR5/genetics, Young Adult
Pubmed
Web of science
Création de la notice
01/03/2012 16:14
Dernière modification de la notice
03/03/2018 21:53
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